Significance of nitric oxide in ionomycin-evoked [3H] GABA release from mouse cerebral cortical neurons *
Functional significance of nitric oxide (NO) in ionomycin-evoked [3 H] γ -aminobutyric acid (GABA) release was investigated using primary culture of mouse cerebral cortical neurons. Ionomycin increased [3 H] GABA release in a dose-dependent manner. This stimulatory action of ionomycin on [3 H] GABA release was dose-dependently inhibited by hemoglobin, a NO scavenger, and a NO synthase inhibitor, NG -methyl-L-arginine, suggesting that the ionomycinevoked [3 H] GABA release from the neurons is mediated by NO production. Inhibitors for Na+ dependent carrier-mediated GABA transport, nipecotic acid and l-(2-(((diphenylmethylene) amino) oxy) ethyl) -1, 2, 5, 6-tetrahydro-3-pyridine-carboxylic acid (NO-711) , reduced the ionomycin-evoked [3 H] GABA release by about 50% . Similarly, the release was also reduced by about 50% in the concomitant presence of ω-agatoxin VIA, an inhibitor specific for P/Q type voltage-dependent Ca2+ channel (VDCC) , and nifedipine, an inhibitor for L-type VDCC. Either nipecotic acid or NO-711 completely abolished the ionomycin-evoked [3 H] GABA release in the presence of these two inhibitors for VDCC. In addition, a hydroxyl radical scavenger, dimethylthiourea, dose-dependently facilitated the ionomycin-evoked [3 H] GABA release. These effects observed in the presence of Na+-dependent carrier-mediated GABA transport inhibitors, inhibitors for VDCC, and dimethylthiourea were similar to NO-induced effects previously reported. These results lead to the conclusion that the ionomycin-evoked [3 H] GABA release is mediated via the formation of NO. (Accepted on March 11, 2000) Kawasaki Igakkaishi 26(1) : 13-23, 2000
